This invention relates to an improved process for the preparation of .omega.-amino-1-hydroxyalkylidene-1,1-bisphosphonic acids of the formula (1) indicated below, where the end products are obtained in a particularly pure form. ##STR2##
It is known according to DE AS 21 30 794 to prepare 3-amino-hydroxypropylidene-1,1-bisphosphonic acid by the reaction of .beta.-alanine with phosphorous acid and phosphorous trichloride and subsequent hydrolysis by the addition of water. But when this procedure is used in the reaction of 4-aminobutyric acid with H.sub.3 PO.sub.3 /PCl.sub.3 and subsequent hydrolysis after the addition of water, a phosphonic acid mixture is obtained, as it can be determined by chromatographic tests.
This phosphonic acid mixture is substantially stable even if the solution is boiled for several hours. When boiling with 30% sodium hydroxide solution, the phosphonic acid mixture is likewise stable.
In practice, phosphonic acids according to Formula I could, therefore, not be obtained in pure form according to the known procedure without great expenditures.
Similar is the situation in the phosphonylation of 6-aminohexanoic acid. Here, too, a reaction mixture is obtained after hydrolysis which contains several different phosphonic acids.
Other processes for the production of 3-aminohydroxypropylidene-1,1-bisphosphonic acid by reaction of a .beta.-alanine with a phosphonating agent under various conditions and subsequent hydrolysis with water, have been reported in DE-AS No. 2,658,961, DE-OS No. 2702631 and our copending U.S. patent application Ser. No. 192,733, filed Oct. 1, 1980, now U.S. Pat. No. 327,039.